ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP
Abstract Metabolic reprogramming is considered one of the hallmarks of cancer in which cancer cells reprogram some of their metabolic cascades, mostly driven by the specific chemical microenvironment in cancer tissues. The altered metabolic pathways are increasingly being considered as potential tar...
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| Format: | Article |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-02249-z |
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| author | Liang Sun Ting Lu Linhua Jiang Huihui Yao Qixuan Xu Jie Sun Xiaoqin Yang Songbing He Xinguo Zhu |
| author_facet | Liang Sun Ting Lu Linhua Jiang Huihui Yao Qixuan Xu Jie Sun Xiaoqin Yang Songbing He Xinguo Zhu |
| author_sort | Liang Sun |
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| description | Abstract Metabolic reprogramming is considered one of the hallmarks of cancer in which cancer cells reprogram some of their metabolic cascades, mostly driven by the specific chemical microenvironment in cancer tissues. The altered metabolic pathways are increasingly being considered as potential targets for cancer therapy. In this view, Aldolase A (ALDOA), a key glycolytic enzyme, has been validated as a candidate oncogene in several cancers. The current study aimed to investigate the role of ALDOA in the initiation and development of colorectal cancer (CRC). In this study, we observed an elevated expression of ALDOA in human CRC tissues and a positive correlation of elevated ALDOA expression with tumor size, invasion depth, LNM, and TNM stage. Kaplan–Meier analysis revealed that elevated ALDOA levels correlated with a poor prognosis in CRC patients with stage I-III, whereas the prognosis tends to be favorable in patients with advanced CRC. In addition, loss of function and gain of function experiments showed that ALDOA promoted CRC cell proliferation and migration in vitro and in vivo. Mechanistically, high ALDOA expression inhibited AMP-activated protein kinase (AMPK) phosphorylation possibly through regulating cellular glycolysis or the formation of v-ATPase-regulator-AXIN/LKB1 complex, which led to Yes-associated protein (YAP) unphosphorylation and enhanced the proliferative and migratory potential of CRC cells. Finally, the positive correlation between ALDOA and YAP signaling was also confirmed in clinical CRC tissues and the public data. Herein, ALDOA was identified to be a new metabolic regulator of YAP that suppresses the activation of AMPK signaling. This could suggest a novel avenue for treating CRC by inhibiting both ALDOA and YAP signaling. |
| format | Article |
| id | doaj-art-15e545cb4d7b4e80b1bc26a9c80605ad |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-15e545cb4d7b4e80b1bc26a9c80605ad2025-01-05T12:08:45ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0110111510.1038/s41420-024-02249-zALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAPLiang Sun0Ting Lu1Linhua Jiang2Huihui Yao3Qixuan Xu4Jie Sun5Xiaoqin Yang6Songbing He7Xinguo Zhu8Department of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Ultrasound, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversitySchool of Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityAbstract Metabolic reprogramming is considered one of the hallmarks of cancer in which cancer cells reprogram some of their metabolic cascades, mostly driven by the specific chemical microenvironment in cancer tissues. The altered metabolic pathways are increasingly being considered as potential targets for cancer therapy. In this view, Aldolase A (ALDOA), a key glycolytic enzyme, has been validated as a candidate oncogene in several cancers. The current study aimed to investigate the role of ALDOA in the initiation and development of colorectal cancer (CRC). In this study, we observed an elevated expression of ALDOA in human CRC tissues and a positive correlation of elevated ALDOA expression with tumor size, invasion depth, LNM, and TNM stage. Kaplan–Meier analysis revealed that elevated ALDOA levels correlated with a poor prognosis in CRC patients with stage I-III, whereas the prognosis tends to be favorable in patients with advanced CRC. In addition, loss of function and gain of function experiments showed that ALDOA promoted CRC cell proliferation and migration in vitro and in vivo. Mechanistically, high ALDOA expression inhibited AMP-activated protein kinase (AMPK) phosphorylation possibly through regulating cellular glycolysis or the formation of v-ATPase-regulator-AXIN/LKB1 complex, which led to Yes-associated protein (YAP) unphosphorylation and enhanced the proliferative and migratory potential of CRC cells. Finally, the positive correlation between ALDOA and YAP signaling was also confirmed in clinical CRC tissues and the public data. Herein, ALDOA was identified to be a new metabolic regulator of YAP that suppresses the activation of AMPK signaling. This could suggest a novel avenue for treating CRC by inhibiting both ALDOA and YAP signaling.https://doi.org/10.1038/s41420-024-02249-z |
| spellingShingle | Liang Sun Ting Lu Linhua Jiang Huihui Yao Qixuan Xu Jie Sun Xiaoqin Yang Songbing He Xinguo Zhu ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP Cell Death Discovery |
| title | ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP |
| title_full | ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP |
| title_fullStr | ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP |
| title_full_unstemmed | ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP |
| title_short | ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP |
| title_sort | aldoa contributes to colorectal tumorigenesis and metastasis by targeting yap |
| url | https://doi.org/10.1038/s41420-024-02249-z |
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